1. Field of the Invention
This invention relates to a coating for implantable devices, such as an expandable intraluminal prosthesis, one example of which includes a stent. Moreover, the invention is directed to a composition for coating an implantable device.
2. Description of the Related Art
Percutaneous transluminal coronary angioplasty (PTCA) is a procedure for treating heart disease. A catheter assembly having a balloon portion is introduced percutaneously into the cardiovascular system of a patient via the brachial or femoral artery. The catheter assembly is advanced through the coronary vasculature until the balloon portion is positioned across the occlusive lesion. Once in position across the lesion, the balloon is inflated to a predetermined size to radially compress the atherosclerotic plaque of the lesion against the inner wall of the artery to dilate the lumen. The balloon is then deflated to a smaller profile to allow the catheter to be withdrawn from the patient""s vasculature.
A problem associated with the above procedure includes formation of intimal flaps or torn arterial linings which can collapse and occlude the conduit after the balloon is deflated. Moreover, thrombosis and restenosis of the artery may develop over several months after the procedure, which may require another angioplasty procedure or a surgical by-pass operation. To reduce the partial or total occlusion of the artery by the collapse of arterial lining and to reduce the chance of the development of thrombosis and restenosis, an expandable intraluminal prosthesis, one example of which includes a stent, is implanted in the lumen to maintain the vascular patency. Stents are scaffoldings, usually cylindrical or tubular in shape, which function to physically hold open and, if desired, to expand the wall of the passageway. Typically stents are capable of being compressed, so that they can be inserted through small cavities via small catheters, and then expanded to a larger diameter once they are at the desired location. Examples in patent literature disclosing stents which have been successfully applied in PTCA procedures include stents illustrated in U.S. Pat. No. 4,733,665 issued to Palmaz, U.S. Pat. No. 4,800,882 issued to Gianturco, and U.S. Pat. No. 4,886,062 issued to Wiktor.
In treating the damaged vasculature tissue and to further fight against thrombosis and restenosis, there is a need for administrating therapeutic substances to the treatment site. For example, anticoagulants, antiplatelets and cytostatic agents are commonly used to prevent thrombosis of the coronary lumen, to inhibit development of restenosis, and to reduce post-angioplasty proliferation of the vascular tissue, respectively. In order to provide an efficacious concentration to the treated site, systemic administration of such medication often produces adverse or toxic side effects for the patient. Local delivery is a preferred method of treatment in that smaller total levels of medication are administered in comparison to systemic dosages, but are concentrated at a specific site. Local delivery thus produces fewer side effects and achieves more effective results.
One commonly applied technique for the local delivery of a drug is through the use of medicated stents. One proposed method provided stents which were seeded with endothelial cells (Dichek, D. A. et al. Seeding of Intravascular Stents With Genetically Engineered Endothelial Cells; Circulation 1989; 80: 1347-1353). Briefly, endothelial cells were seeded onto stainless steel stents and grown until the stents were covered. The cells were therefore able to be delivered to the vascular wall where they provided therapeutic proteins. Another proposed method of providing a therapeutic substance to the vascular wall included use of a heparin-coated metallic stent, whereby a heparin coating was ionically or covalently bonded to the stent. Significant disadvantages associated with the aforementioned methods include significant loss of the therapeutic substance from the body of the stent during delivery and expansion of the stent, and an absolute lack of control of the release rate of the therapeutic substance from the stent.
Another proposed method involved the use of a polymeric carrier coated onto the surface of a stent, as disclosed in U.S. Pat. No. 5,464,650 issued to Berg et al. Berg disclosed applying to a stent body a solution which included a specified solvent, a specified polymer dissolved in the solvent, and a therapeutic substance dispersed in the blend. The solvent was allowed to evaporate, leaving on the stent surface a coating of the polymer and the therapeutic substance impregnated in the polymer. Among the specified, suitable choices of polymers listed by Berg, empirical results were specifically provided for poly(caprolactone) and poly(L-lactic acid). The preferred choice of mutually compatible solvents included acetone or chloroform. As indicated by Berg, stents where immersed in the solution 12 to 15 times or sprayed 20 times. The evaporation of the solvent provided a white coating. A white coloration is generally indicative of a brittle polymeric coating. A brittle polymeric coating is an undesirable characteristic, since portions of the coating typically become detached during stent expansion. Detachment of the coating causes the quantity of the therapeutic substance to fall below a threshold level sufficient for the effective treatment of a patient.
Accordingly, it is desirable to provide an improved coating that is susceptible to expanding with a prosthesis without significant detachment from the surface of the prosthesis. It is also desirable for the polymer to be able to strongly adhere to the surface of the prosthesis, thereby preventing loss of the polymeric coating during prosthesis delivery. Other desirable features include, but are not limited to, a polymeric coating which allows for a significant control of the release rate of a therapeutic substance, a polymeric coating that can serve as an under-layer for substances which do not easily or effectively bind or adhere to the surface of the prosthesis, a polymeric solution which need not be applied excessively to the surface of the prosthesis to form a coating of a suitable thickness, and a polymeric solution that can be uniformly applied to the surface of the prosthesis.
In accordance with one embodiment of the present invention, a method for forming a coating onto a surface of a prosthesis, e.g., a stent, is provided. In one embodiment, the method comprises applying to the surface of the prosthesis a composition which includes an ethylene vinyl alcohol copolymer and a dimethylsulfoxide solution. The ethylene vinyl alcohol copolymer can constitute from about 0.1% to about 35%, usefully from about 12% to about 20% by weight of the total weight of the composition and the dimethylsulfoxide solution can constitute from about 65% to about 99.9%, usefully from about 80% to about 88% by weight of the total weight of the composition.
In accordance with another embodiment, a fluid can be added to the composition which can enhance the wetting of the composition. To enhance the wetting of the composition, a suitable fluid typically has a high capillary permeation. A suitably high capillary permeation corresponds to a contact angle less than about 90xc2x0. The wetting fluid can have a viscosity not greater than about 50 centipoise. The wetting fluid, accordingly, when added to the composition, reduces the viscosity of the composition. The wetting fluid should be mutually compatible with the ethylene vinyl alcohol copolymer and dimethylsulfoxide solution and should not precipitate the copolymer. Useful examples of the wetting fluid include, but are not limited to, tetrahydrofuran (THF), dimethylformamide (DMF), 1-butanol, n-butyl acetate, and mixtures thereof. In this embodiment, the ethylene vinyl alcohol copolymer can constitute from about 0.1% to about 35%, usefully from about 10% to about 25% by weight of the total weight of the composition, the dimethylsulfoxide can constitute from about 19.9% to about 98.9%, usefully from about 50% to about 79% by weight of the total weight of the composition, the wetting fluid can constitute from about 1% to about 80%, usefully from about 5% to about 40% by weight of the total weight of the composition.
In accordance with another embodiment, sufficient amounts of a therapeutic substance or a combination of substances are dispersed in the blended composition of the ethylene vinyl alcohol copolymer and the dimethylsulfoxide solution. In this embodiment, the ethylene vinyl alcohol copolymer can constitute from about 0.1% to about 35%, usefully from about 12% to about 20% by weight of the total weight of the composition, the dimethylsulfoxide solution can constitute from about 59.9% to about 99.8%, usefully from about 79% to about 87% by weight of the total weight of the composition, and the therapeutic substance can constitute from about 0.1% to about 40%, usefully from about 1% to about 9% by weight of the total weight of the composition.
In accordance with another embodiment, sufficient amounts of a therapeutic substance or combination of substances are dispersed in the blended composition of the ethylene vinyl alcohol copolymer, the dimethylsulfoxide solution, and a wetting fluid. In this embodiment, the ethylene vinyl alcohol copolymer can constitute from about 0.1% to about 35%, usefully from about 10% to about 25% by weight of the total weight of the composition, the dimethylsulfoxide solution can constitute from about 19.8% to about 98.8%, usefully from about 49% to about 79% by weight of the total weight of the composition, the wetting fluid can constitute from about 1% to about 80%, usefully from about 5% to about 40% by weight of the total weight of the composition, and the therapeutic substance can constitute from about 0.1% to about 40%, usefully from about 1% to about 9% by weight of the total weight of the composition.
The composition can be applied to the prosthesis simply by immersing the prosthesis into the composition or by spraying the composition onto the surface of the prosthesis. The dimethylsulfoxide solution or the combination of the dimethylsulfoxide solution and wetting fluid is removed from the composition which is applied to the surface of the prosthesis. The copolymer, with or without the therapeutic substance, solidifies and adheres to the surface of the prosthesis. One technique for removing the dimethylsulfoxide solution or combination of the dimethylsulfoxide solution and wetting fluid includes allowing the components to evaporate to a substantial elimination, for example, by heating the prosthesis at a predetermined temperature for a predetermined duration of time.
In accordance with another embodiment, a layer comprising a polymeric material, without a therapeutic substance, can be formed on the therapeutic substance impregnated ethylene vinyl alcohol coating. The layer can be any suitable polymeric material, including an ethylene vinyl alcohol copolymer. The layer provides a rate reducing membrane for therapeutic substances that may be quickly released from the coating.
In accordance with another embodiment of the invention a coating for a prosthesis is provided. In one embodiment, the coating comprises an ethylene vinyl alcohol copolymer. The ethylene vinyl alcohol copolymer can serve as a primer, allowing substances, such as a variety of biocompatible polymers, to be effectively secured by the prosthesis.
In accordance to another embodiment, the coating comprises an ethylene vinyl alcohol copolymer and a therapeutic substance carried by the copolymer. The coating allows the therapeutic substance to be retained onto the prosthesis during delivery and, if applicable, expansion and also allows for a sustained release of the substance at the site of implantation. Therapeutic substances such as antineoplastics, antiinflammatories, antiplatelets, anticoagulants, antifibrins, antithrombins, antimitotics, antiproliferatives, antibiotics, antioxidants, antiallergics, and combinations thereof can be carried by the copolymer.